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Experimental Therap...
Experimental Therapy of HER2-Expressing Xenografts Using the Second-Generation HER2-Targeting Affibody Molecule 188Re-ZHER2:41071
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- Liu, Yongsheng (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Vorobyeva, Anzhelika (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Orlova, Anna, 1960- (författare)
- Uppsala universitet,Theranostics
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- Konijnenberg, Mark W. (författare)
- Erasmus MC, Dept Radiol & Nucl Med, NL-3000 CA Rotterdam, Netherlands.
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- Xu, Tianqi (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Bragina, Olga (författare)
- Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.
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- Loftenius, Annika (författare)
- Affibody AB, S-17165 Solna, Sweden.
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- Rosander, Erica (författare)
- Affibody AB, S-17165 Solna, Sweden.
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- Frejd, Fredrik Y. (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap,Affibody AB, S-17165 Solna, Sweden
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- Tolmachev, Vladimir (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap,Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia
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(creator_code:org_t)
- 2022-05-20
- 2022
- Engelska.
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Ingår i: Pharmaceutics. - : MDPI. - 1999-4923. ; 14:5
- Relaterad länk:
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https://doi.org/10.3...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- HER2-targeted radionuclide therapy might be helpful for the treatment of breast, gastric, and ovarian cancers which have developed resistance to antibody and antibody-drug conjugate-based therapies despite preserved high HER2-expression. Affibody molecules are small targeting proteins based on a non-immunoglobulin scaffold. The goal of this study was to test in an animal model a hypothesis that the second-generation HER2-targeting Affibody molecule 188Re-ZHER2:41071 might be useful for treatment of HER2-expressing malignant tumors. ZHER2:41071 was efficiently labeled with a beta-emitting radionuclide rhenium-188 (188Re). 188Re-ZHER2:41071 demonstrated preserved specificity and high affinity (KD = 5 ± 3 pM) of binding to HER2-expressing cells. In vivo studies demonstrated rapid washout of 188Re from kidneys. The uptake in HER2-expressing SKOV-3 xenografts was HER2-specific and significantly exceeded the renal uptake 4 h after injection and later. The median survival of mice, which were treated by three injections of 16 MBq 188Re-ZHER2:41071 was 68 days, which was significantly longer (<0.0001 in the log-rank Mantel-Cox test) than survival of mice in the control groups treated with vehicle (29 days) or unlabeled ZHER2:41071 (27.5 days). In conclusion, the experimental radionuclide therapy using 188Re-ZHER2:41071 enabled enhancement of survival of mice with human tumors without toxicity to the kidneys, which is the critical organ.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
Nyckelord
- HER2
- radionuclide therapy
- affibody molecule
- rhenium-188
- second-generation scaffold
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Liu, Yongsheng
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Vorobyeva, Anzhe ...
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Orlova, Anna, 19 ...
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Konijnenberg, Ma ...
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Xu, Tianqi
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Bragina, Olga
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visa fler...
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Loftenius, Annik ...
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Rosander, Erica
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Frejd, Fredrik Y ...
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Tolmachev, Vladi ...
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Radiologi och bi ...
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Pharmaceutics
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Uppsala universitet